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Biomarker discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric acid ratio in urine and plasma as potential markers |
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| Authors: | Hidenori Kamiguchi Mika Murabayashi Ikuo Mori Akira Horinouchi Kazutaka Higaki |
| Institution: | 1. Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan;2. Process Chemistry, Pharmaceutical Science, Takeda Pharmaceutical Company Limited, Osaka, Japan;3. PS Administration Department, Pharmaceutical Science, Takeda Pharmaceutical Company Limited, Osaka, Japan;4. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan |
| Abstract: | Context: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable. Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach. Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs. Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation. Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis. |
| Keywords: | Phenylacetylglycine hippuric acid drug-induced phospholipidosis phenylalanine metabolism |